title: A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence.
abstract: BACKGROUND
  Topiramate increases GABAergic activity and antagonizes the AMPA/kainate subtype of glutamate receptors. Through these mechanisms of action, topiramate may reduce alcohol and cocaine reward and may reduce alcohol and cocaine craving. Topiramate has been shown to reduce drinking in persons with alcohol dependence, and reduce relapse in stimulant-dependent patients. The current trial was intended to test the ability of topiramate to promote cocaine and alcohol abstinence among patients addicted to both drugs.
  
  
  METHODS
  The study was a double-blind, placebo-controlled, 13-week trial involving 170 cocaine and alcohol dependent subjects. After achieving a period of cocaine and alcohol abstinence, subjects were randomized to topiramate, 300 mg daily, or identical placebo capsules. In addition, subjects received weekly individual psychotherapy. Primary outcome measures included self-reported alcohol and cocaine use, and thrice weekly urine drug screens. Secondary outcome measures included cocaine and alcohol craving, Addiction Severity Index results, cocaine withdrawal symptoms, and clinical global improvement ratings.
  
  
  RESULTS
  Topiramate was not better than placebo in reducing cocaine use on the a priori primary outcome measure, or in reducing alcohol use. Topiramate was not better than placebo in reducing cocaine craving. Topiramate-treated subjects, compared to placebo-treated subjects, were more likely to be retained in treatment and more likely to be abstinent from cocaine during the last three weeks of the trial. Subjects who entered treatment with more severe cocaine withdrawal symptoms responded better to topiramate.
  
  
  CONCLUSIONS
  Topiramate plus cognitive behavioral therapy may reduce cocaine use for some patients with comorbid cocaine and alcohol dependence.
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3900 Chestnut Street, Philadelphia, PA 19104, USA. Electronic address: kampman@upenn.edu.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Kampman
authors.forename: Helen M
authors.initials: HM
authors.lastname: Pettinati
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Lynch
authors.forename: Kelly
authors.initials: K
authors.lastname: Spratt
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wierzbicki
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D000927:Anticonvulsants / Q000627:therapeutic use; D016739:Behavior, Addictive / Q000188:drug therapy; D019970:Cocaine-Related Disorders / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D055502:Secondary Prevention; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose
keywords: Alcohol; Clinical trial; Cocaine; Placebo; Topiramate